RO-32-3555, AN ORALLY-ACTIVE COLLAGENASE SELECTIVE INHIBITOR, PREVENTS STRUCTURAL DAMAGE IN THE STR ORT MOUSE MODEL OF OSTEOARTHRITIS/

Objective. To determine the efficacy of:a selective inhibitor of colla genases in an animal model of osteoarthritis (OA). Methods. Ro 32-3555 , an orally active collagenase selective inhibitor, was administered t o STR/ORT mice. Microfocal x-ray-generated images of the hind limbs we re visually scored for joint space narrowing, osteophyte formation, an d calcification of tendons. Histologic sections of the knees were scor ed for cartilage changes including loss of surface matrix, fibrillatio n, and eburnation. Results, Significant inhibition of joint space narr owing and osteophyte formation was achieved in groups of animals treat ed with 10-50 mg/kg(-1) of Ro 32-3555, These effects were confirmed hi stologically in the same groups of animals: histologic analysis reveal ed that Ro 32-3555 protected cartilage from degradative changes. Concl usion. Ro 32-3555, a collagenase selective inhibitor, inhibits both th e cartilage and bone changes in this mouse model of OA, and thus shows great potential as a treatment of OA in humans.